The weapon:
The sword is definitely the best weapon. It deals a lot of damage and you can upgrade it with sword wind to get a range attack, too. (Update: don't pick sword wind)

The Skill:
The skill "Charge" is just OP. You get a massive speedboost, invincibility, and the shield around you deals damage on contact. The strategy is to get the upgrade "vampirism". At the beginning of every round, activate the skill and rush the enemies by charging at them and dealing damage with the sword and the shield. You regenerate a lot of health + kill many enemies early in the round. If there is only 1 enemy left, wait until your skill is realoaded, then kill the last enemy with the sword. That's important, because you'll need to activate charge at the beginning of the next round.

The Upgrades:
Choose vampirism as early as possible. Longer Charge is important too, but don't choose bigger Charge-shield.
Damage up and Speed up are important, of course, choose them if needed. (Your goal is to have at least as much attack damage as the enemies max health in order to kill them as quick as possible)

You beat the game if you beat lvl 45. The game doesn't get harder, because you can choose damage up every round and you'll always onehit the enemies.

The upgrade +50% HP is useful too, if you have many HP. You can choose it, even if you are full health, you'll get the Healthboost as an overheal (non-regenerable HP over the limit of your HP).
(Update: the overheal doesn't exist anymore)

At this point, you can't die if you don't want to. You can heal every beginning of every new round, you'll always onehit enemies and they can't kill you because you are practically a block of concrete.

Enjoy it.
If there are any questions, pls contact me per comments.